Leprosy exposure, infection and disease: a 25-year surveillance study of leprosy patient contacts

Contact surveillance is a valuable strategy for controlling leprosy. A dynamic cohort study of leprosy contacts was initiated in 1987 at Oswaldo Cruz Foundation. The objective of this work was to review the data on the major risk factors leading up to the infectious stage of the disease, estimate incidence rates of leprosy in the cohort and characterise the risk factors for the disease among the contacts under surveillance. The incidence rate of leprosy among contacts of leprosy patients was estimated at 0.01694 cases per person-year in the first five years of follow-up. The following factors were associated with acquiring the disease: (i) not receiving the BCG vaccine, (ii) a negative Mitsuda reaction and (iii) contact with a patient with a multibacillary clinical form of leprosy. The contacts of index patients who had high bacilloscopic index scores > 1 were at especially high risk of infection. The following factors were associated with infection, which was defined as a seropositive reaction for anti-phenolic glicolipid-1 IgM: (i) young age (< 20 years), (ii) a low measured Mitsuda reaction (< 5 mm) and (iii) contact with an index patient who had a high bacilloscopic index. BCG vaccination and re-vaccination were shown to be protective among household contacts. The main conclusions of this study indicate an urgent need for additional leprosy control strategies in areas with a high incidence of the disease.

R-ESHAP as salvage therapy for patients with relapsed or refractory diffuse large B-cell lymphoma: the influence of prior exposure to rituximab on outcome. A GEL/TAMO study.

BACKGROUND The role of re-treatment with rituximab in aggressive B-cell lymphomas still needs to be defined. This study evaluated the influence of prior exposure to rituximab on response rates and survival in patients with diffuse large B-cell lymphoma treated with rituximab plus etoposide, cytarabine, cisplatinum and methylprednisolone (R-ESHAP). DESIGN AND METHODS We retrospectively analyzed 163 patients with relapsed or refractory diffuse large B-cell lymphoma who received R-ESHAP as salvage therapy with a curative purpose. Patients were divided into two groups according to whether rituximab had been administered (n=94, "R+" group) or not (n=69, "R-" group) prior to R-ESHAP. RESULTS Response rates were significantly higher in the R- group in the univariate but not in the multivariate analysis. In the analysis restricted to the R+ group, we observed very low complete remission and overall response rates in patients with primary refractory disease (8% and 33%, respectively), as compared to those in patients who were in first partial remission (41% and 86%) or who had relapsed disease (50% and 75%) (p<0.01 in both cases). Overall, 60% and 65% of patients in the R+ and R- groups, respectively, underwent stem-cell transplantation after the salvage therapy. With a median follow-up of 29 months (range, 6-84), patients in the R+ group had significantly worse progression-free survival (17% vs. 57% at 3 years, p<0.0001) and overall survival (38% v 67% at 3 years, p=0.0005) than patients in the R- group. Prior exposure to rituximab was also an independent adverse prognostic factor for both progression-free survival (RR: 2.0; 95% CI: 1.2-3.3, p=0.008) and overall survival (RR: 2.2; 95% CI: 1.3-3.9, p=0.004). CONCLUSIONS R-ESHAP was associated with a high response rate in patients who were not refractory to upfront rituximab-based chemotherapy. However, the survival outcome was poor for patients previously exposed to rituximab, as compared to in those who had not previously been treated with rituximab.

Individual monitoring of internal exposure for nuclear medicine workers in Switzerland.

Monitoring of internal exposure for nuclear medicine workers requires frequent measurements due to the short physical half-lives of most radionuclides used in this field. The aim of this study was to develop screening measurements performed at the workplace by local staff using standard laboratory instrumentation, to detect whether potential intake has occurred. Such measurements do not enable to determine the committed effective dose, but are adequate to verify that a given threshold is not exceeded. For radioiodine, i.e. (123)I, (124)I, (125)I and (131)I, a calibrated surface contamination monitor is placed in front of the thyroid to detect whether the activity threshold has been exceeded. For radionuclides with very short physical half-lives (≤6 h), such as (99m)Tc and those used in positron emission tomography  imaging, i.e. (11)C, (15)O, (18)F and (68)Ga, screening procedures consist in performing daily measurements of the ambient dose rate in front of the abdomen. Other gamma emitters used for imaging, i.e. (67)Ga, (111)In and (201)Tl, are measured with a scintillation detector located in front of the thorax. For pure beta emitters, i.e. (90)Y and (169)Er, as well as beta emitters with low-intensity gamma rays, i.e. (153)Sm, (177)Lu, (186)Re and (188)Re, the procedure consists in measuring hand contamination immediately after use. In Switzerland, screening procedures have been adopted by most nuclear medicine services since such measurements enable an acceptable monitoring while taking into account practical and economic considerations.

Effects of acute versus repeated cocaine exposure on the expression of endocannabinoid signaling-related proteins in the mouse cerebellum.

Growing awareness of cerebellar involvement in addiction is based on the cerebellum's intermediary position between motor and reward, potentially acting as an interface between motivational and cognitive functions. Here, we examined the impact of acute and repeated cocaine exposure on the two main signaling systems in the mouse cerebellum: the endocannabinoid (eCB) and glutamate systems. To this end, we investigated whether eCB signaling-related gene and protein expression {cannabinoid receptor type 1 receptors and enzymes that produce [diacylglycerol lipase alpha/beta (DAGLα/β) and N-acyl phosphatidylethanolamine phospholipase D (NAPE-PLD)] and degrade [monoacylglycerol lipase (MAGL) and fatty acid amino hydrolase (FAAH)] eCB} were altered. In addition, we analyzed the gene expression of relevant components of the glutamate signaling system [glutamate synthesizing enzymes liver-type glutaminase isoform (LGA) and kidney-type glutaminase isoform (KGA), metabotropic glutamatergic receptor (mGluR3/5), NMDA-ionotropic glutamatergic receptor (NR1/2A/2B/2C) and AMPA-ionotropic receptor subunits (GluR1/2/3/4)] and the gene expression of tyrosine hydroxylase (TH), the rate-limiting enzyme in catecholamine biosynthesis, because noradrenergic terminals innervate the cerebellar cortex. Results indicated that acute cocaine exposure decreased DAGLα expression, suggesting a down-regulation of 2-arachidonylglycerol (2-AG) production, as well as gene expression of TH, KGA, mGluR3 and all ionotropic receptor subunits analyzed in the cerebellum. The acquisition of conditioned locomotion and sensitization after repeated cocaine exposure were associated with an increased NAPE-PLD/FAAH ratio, suggesting enhanced anandamide production, and a decreased DAGLβ/MAGL ratio, suggesting decreased 2-AG generation. Repeated cocaine also increased LGA gene expression but had no effect on glutamate receptors. These findings indicate that acute cocaine modulates the expression of the eCB and glutamate systems. Repeated cocaine results in normalization of glutamate receptor expression, although sustained changes in eCB is observed. We suggest that cocaine-induced alterations to cerebellar eCB should be considered when analyzing the adaptations imposed by psychostimulants that lead to addiction.

Freedom Trial First-Year Extension: Results from 4 Years of Denosumab Exposure in Women with Postmenopausal Osteoporosis

Aims: To investigate the long-term efficacy and safety of denosumab (DMAb) for the treatment of postmenopausal women with osteoporosis in an open-label extension to the 3-year FREEDOM study.1Methods: All women who completed the FREEDOM study were eligible to enter a long-term open-label extension (up to 10 years). After providing informed consent, participants received 6-monthly subcutaneous injections of DMAb (60 mg). Here we report data from the first year of followup. For women randomized to DMAb in the FREEDOM study ('long-term group'), this represents up to 48 months of DMAb exposure (eight 6-monthly injections). For those randomized to placebo ('de novo group') the data are from up to 12 months of exposure (two injections). All participants continued to take calcium (1 g) and vitamin D (≥400 IU) supplements daily. Changes in bone mineral density (BMD) and bone turnover markers (BTM) are reported for subjects enrolled in the extension. No formal statistical testing was planned for this interim report. P-values are descriptive.Results: Overall, 4,550 eligible women (70.2%) who completed the FREEDOM study entered the open-label extension study (long-term, n=2,343; de novo, n=2,207). During the first year of the extension, lumbar spine (LS) BMD in the long-term group further increased by 2.0% (12.1% increase vs. FREEDOM baseline at 48 months), and total hip (TH) BMD further increased by 0.8% (6.5% increase at 48 months) (p<0.0001 for both BMD gains during year 4; Fig. 1). During the first year of the extension, LS and TH BMD increased by 5.4% and 3.0%, respectively in the de novo group (both p<0.0001). After DMAb initiation, serum C-telopeptide (CTX) in the de novo group decreased rapidly and similarly to the long-term group (Fig. 2). Reductions in BTMs continue to attenuate at the end of the dosing interval as previously reported. Adverse event (AE) rates were similar (70.4% of women in the longterm group and 67.9% in the de novo group). Serious Aes were also similar (9.8% and 11.2% of women, respectively). During year 4, osteoporotic nonvertebral fractures were reported in 31 women in the long-term group and 51 in the denovo group.Fig. 1. Percentage change in BMD with denosumab for4 years (long-term) or 1 year (de novo)Fig. 2. Percentage change in sCTX over timeConclusions: These interim results suggest that continuation of DMAb treatment through 48 months is associated with further significant increases in spine and hip BMD with sustained reduction of bone turnover. The de-novo treatment group results confirm the first year active treatment findings previously reported1.Acknowledgements: Amgen Inc. sponsored this study. Figure ©2010, American Society for Bone and Mineral Research, used by permission, all rights reserved. Disclosure of Interest: H. Bone Grant/Research Support from: Amgen, Eli Lilly, Merck, Nordic Bioscience, Novartis, Takeda Pharmaceuticals, Consultant/Speaker's bureau/ Advisory activities with: Amgen, Merck, Takeda Pharmaceuticals, Zelos, S. Papapoulos Consultant/Speaker's bureau/ Advisory activities with: Amgen, Merck, Novartis, Lilly, Procter and Gamble, GSK, M.-L. Brandi Grant/Research Support from: MSD, GSK, Nycomed, NPS, Amgen, J. Brown Grant/Research Support from: Abbott, Amgen, Bristol Myers Squibb, Eli Lilly, Pfizer, Roche, Consultant/ Speaker's bureau/Advisory activities with: Abbott, Amgen, Eli Lilly, Novartis, Merck, Warner Chilcott,, R. Chapurlat Grant/Research Support from: Servier, Sanofi-Aventis, Warner-Chilcott, Novartis, Merck, Consultant/Speaker's bureau/Advisory activities with: Servier, Novartis, Amgen, E. Czerwinski: None Declared, N. Daizadeh Employee of: Amgen Inc., Stock ownership or royalties of: Amgen Inc., A. Grauer Employee of: Amgen Inc., Stock ownership or royalties of: Amgen Inc., C. Haller Employee of: Amgen Inc., Stock ownership or royalties of: Amgen Inc., M.-A. Krieg: None Declared, C. Libanati Employee of: Amgen Inc., Stock ownership or royalties of: Amgen Inc., Z. Man Grant/Research Support from: Amgen, D. Mellström: None Declared, S. Radominski Grant/Research Support from: Amgen, Pfizer, Roche, BMS, J.-Y. Reginster Grant/Research Support from: Bristol Myers Squibb, Merck Sharp & Dohme, Rottapharm, Teva, Lilly, Novartis, Roche, GlaxoSmithKline, Amgen, Servier, Consultant/Speaker's bureau/ Advisory activities with: Servier, Novartis, Negma, Lilly,Wyeth, Amgen, GlaxoSmithKline, Roche, Merckle, Nycomed, NPS, Theramex, UCB, Merck, Sharpe & Dohme, Rottapharm, IBSA, Genvrier, Teijin, Teva, Ebewee Pharma, Zodiac, Analis, Theramex, Novo-Nordisk, H. Resch: None Declared, J. A. Román Grant/Research Support from: Roche, Pharma, C. Roux Grant/Research Support from: Amgen, MSD, Novartis, Servier, Roche, Consultant/ Speaker's bureau/Advisory activities with: Amgen, MSD, Novartis, Servier, Roche, S. Cummings Grant/ Research Support from: Amgen, Lilly, Consultant/Speaker's bureau/Advisory activities with: Amgen, Lilly, Novartis, Merck

Estimation de la fonction rénale par l'equation MDRD: intérêt et limites pour l'adaptation des doses de médicaments [Renal function estimation by MDRD equation: interest and limitations for drug dosing].

The MDRD (Modification of diet in renal disease) equation enables glomerular filtration rate (GFR) estimation from serum creatinine only. Thus, the laboratory can report an estimated GFR (eGFR) with each serum creatinine assessment, increasing therefore the recognition of renal failure. Predictive performance of MDRD equation is better for GFR < 60 ml/min/1,73 m2. A normal or near-normal renal function is often underestimated by this equation. Overall, MDRD provides more reliable estimations of renal function than the Cockcroft-Gault (C-G) formula, but both lack precision. MDRD is not superior to C-G for drug dosing. Being adjusted to 1,73 m2, MDRD eGFR has to be back adjusted to the patient's body surface area for drug dosing. Besides, C-G has the advantage of a greater simplicity and a longer use.

Development of a retrospective job exposure matrix for PCB-exposed workers in capacitor manufacturing

Objectives: Polychlorinated biphenyls (PCBs) are considered probable human carcinogens by the International Agency for Research on Cancer and one congener, PCB126, has been rated as a known human carcinogen. A period-specific job exposure matrix (JEM) was developed for former PCB-exposed capacitor manufacturing workers (n=12,605) (1938-1977). Methods: A detailed exposure assessment for this plant was based on a number of exposure determinants (proximity, degree of contact with PCBs, temperature, ventilation, process control, job mobility). The intensity and frequency of PCB exposures by job for both inhalation and dermal exposures, and additional chemical exposures were reviewed. The JEM was developed in nine steps: (1) all unique jobs (n=1,684) were assessed using (2) defined PCB exposure determinants; (3) the exposure determinants were used to develop exposure profiles; (4) similar exposure profiles were combined into categories having similar PCB exposures; (5) qualitative intensity (high-medium-low-baseline) and frequency (continuous-intermittent) ratings were developed, and (6) used to qualitatively rate inhalation and dermal exposure separately for each category; (7) quantitative intensity ratings based on available air concentrations were developed for inhalation and dermal exposures based on equal importance of both routes of exposure; (8) adjustments were made for overall exposure, and (9) for each category the product of intensity and frequency was calculated, and exposure in the earlier era was weighted. Results: A period-specific JEM modified for two eras of stable PCB exposure conditions. Conclusions: These exposure estimates, derived from a systematic and rigorous use of the exposure determinant data, lead to cumulative PCB exposure-response relationships in the epidemiological cancer mortality and incidence studies of this cohort. [Authors]

Modelling short-term ultraviolet exposure as an alternative to individual dosimetry

Background: Excessive exposure to solar Ultra-Violet (UV) light is the main cause of most skin cancers in humans. Factors such as the increase of solar irradiation at ground level (anthropic pollution), the rise in standard of living (vacation in sunny areas), and (mostly) the development of outdoor activities have contributed to increase exposure. Thus, unsurprisingly, incidence of skin cancers has increased over the last decades more than that of any other cancer. Melanoma is the most lethal cutaneous cancer, while cutaneous carcinomas are the most common cancer type worldwide. UV exposure depends on environmental as well as individual factors related to activity. The influence of individual factors on exposure among building workers was investigated in a previous study. Posture and orientation were found to account for at least 38% of the total variance of relative individual exposure. A high variance of short-term exposure was observed between different body locations, indicating the occurrence of intense, subacute exposures. It was also found that effective short-term exposure ranged between 0 and 200% of ambient irradiation, suggesting that ambient irradiation is a poor predictor of effective exposure. Various dosimetric techniques enable to assess individual effective exposure, but dosimetric measurements remain tedious and tend to be situation-specific. As a matter of facts, individual factors (exposure time, body posture and orientation in the sun) often limit the extrapolation of exposure results to similar activities conducted in other conditions. Objective: The research presented in this paper aims at developing and validating a predictive tool of effective individual exposure to solar UV. Methods: Existing computer graphic techniques (3D rendering) were adapted to reflect solar exposure conditions and calculate short-term anatomical doses. A numerical model, represented as a 3D triangular mesh, is used to represent the exposed body. The amount of solar energy received by each "triangle is calculated, taking into account irradiation intensity, incidence angle and possible shadowing from other body parts. The model take into account the three components of the solar irradiation (direct, diffuse and albedo) as well as the orientation and posture of the body. Field measurements were carried out using a forensic mannequin at the Payerne MeteoSwiss station. Short-term dosimetric measurements were performed in 7 anatomical locations for 5 body postures. Field results were compared to the model prediction obtained from the numerical model. Results: The best match between prediction and measurements was obtained for upper body parts such as shoulders (Ratio Modelled/Measured; Mean = 1.21, SD = 0.34) and neck (Mean = 0.81, SD = 0.32). Small curved body parts such as forehead (Mean = 6.48, SD = 9.61) exhibited a lower matching. The prediction is less accurate for complex postures such as kneeling (Mean = 4.13, SD = 8.38) compared to standing up (Mean = 0.85, SD = 0.48). The values obtained from the dosimeters and the ones computed from the model are globally consistent. Conclusion: Although further development and validation are required, these results suggest that effective exposure could be predicted for a given activity (work or leisure) in various ambient irradiation conditions. Using a generic modelling approach is of high interest in terms of implementation costs as well as predictive and retrospective capabilities.

Health effects of occupational exposure to traffic particles and noise

Exposure to fine particles and noise has been linked to cardiovascular diseases and elevated cardiovascular mortality affecting the worldwide population. Residence and/or work in proximity to emission sources as for example road traffic leads to an elevated exposure and a higher risk for adverse health effects. Highway maintenance workers spend most of their work time in traffic and are exposed regularly to particles and noise. The aims of this thesis were to provide a better understanding of the workers' mixed exposure to particles and noise and to assess cardiopulmonary short term health effects in relation to this exposure. Exposure and health data were collected in collaboration with 8 maintenance centers of the Swiss Road Maintenance Services located in the cantons Bern, Fribourg and Vaud in western Switzerland. Repeated measurements with 18 subjects were conducted during 50 non-consecutive work shifts between Mai 2010 and February 2012, equally distributed over all seasons. In the first part of this thesis we tested and validated measurements of ultrafine particles with a miniature diffusion size classifier (miniDiSC) - a novel particle counting device that was used for the exposure assessment during highway maintenance work. We found that particle numbers and average particle size measured by the miniDiSC were highly correlated with data from the P-TRAK, a condensation particle counter (CPC), as well as from a scanning mobility particle sizer (SMPS). However, the miniDiSC measured significantly more particles than the P-TRAK and significantly less than the SMPS in its full size range. Our data suggests that the instrument specific cutoffs were the main reason for the different particle counts. The first main objective of this thesis was to investigate the exposure of highway maintenance workers to air pollutants and noise, in relation to the different maintenance activities. We have seen that the workers are regularly exposed to high particle and noise levels. This was a consequence of close proximity to highway traffic and the use of motorized working equipment such as brush cutters, chain saws, generators and pneumatic hammers during which the highest exposure levels occurred. Although exposure to air pollutants were not critical if compared to occupational exposure limits, the elevated exposure to particles and noise may lead to a higher risk for cardiovascular diseases in this worker population. The second main objective was to investigate cardiopulmonary short-term health effects in relation to the particle and noise exposure during highway maintenance work. We observed a PM2.5 related increase of the acute-phase inflammation markers C-reactive protein and serum amyloid A and a decrease of TNFa. Heart rate variability increased as a consequence of particle as well as noise exposure. Increased high frequency power indicated a stronger parasympathetic influence on the heart. Elevated noise levels during recreational time, after work, were related to increased blood pressure. Our data confirmed that highway maintenance workers are exposed to elevated levels of particles and noise as compared to the average population. This exposure poses a cardiovascular health risk and it is therefore important to make efforts to better protect the workers health. The use of cleaner machines during maintenance work would be a major step to improve the workers' situation. Furthermore, regulatory policies with the aim of reducing combustion and non-combustion emissions from road traffic are important for the protection of workers in traffic environments and the entire population.

Procalcitonin for reduced antibiotic exposure in ventilator-associated pneumonia: a randomised study.

In patients with ventilator-associated pneumonia (VAP), guidelines recommend antibiotic therapy adjustment according to microbiology results after 72 h. Circulating procalcitonin levels may provide evidence that facilitates the reduction of antibiotic therapy. In a multicentre, randomised, controlled trial, 101 patients with VAP were assigned to an antibiotic discontinuation strategy according to guidelines (control group) or to serum procalcitonin concentrations (procalcitonin group) with an antibiotic regimen selected by the treating physician. The primary end-point was antibiotic-free days alive assessed 28 days after VAP onset and analysed on an intent-to-treat basis. Procalcitonin determination significantly increased the number of antibiotic free-days alive 28 days after VAP onset (13 (2-21) days versus 9.5 (1.5-17) days). This translated into a reduction in the overall duration of antibiotic therapy of 27% in the procalcitonin group (p = 0.038). After adjustment for age, microbiology and centre effect, the rate of antibiotic discontinuation on day 28 remained higher in the procalcitonin group compared with patients treated according to guidelines (hazard rate 1.6, 95% CI 1.02-2.71). The number of mechanical ventilation-free days alive, intensive care unit-free days alive, length of hospital stay and mortality rate on day 28 for the two groups were similar. Serum procalcitonin reduces antibiotic therapy exposure in patients with ventilator associated pneumonia.

Topical retinoids exposure during pregnancy.

Concerns have been raised with the topical use of retinoids since the publication of occasional cases associated with characteristic retinoid embryopathy, originally described after oral use. Epidemiological data are still scant. A collaborative study was carried out to evaluate the rate of congenital malformations following 1st trimester topical retinoid exposure. Using a standardized protocol exposed pregnancies and non exposed controls were prospectively recorded by the European Network of Teratology Information Services (ENTIS). A population of 222 pregnant women exposed to topical retinoids (median age [range]: 30 [21 - 42] years; gestational week at call: 7 [3 - 35]) were compared to 444 women not exposed (median age [range]: 32 [17 - 48] years; gestational week at call: 8 [2 - 39]). The following retinoids were identified: adapalene: 22; retinoic acid: 10; tretinoin: 135; isotretinoin:49, others: 6. The exposed and non-exposed groups did not differ in maternal alcohol and tobacco use, gestational duration, birth weight and length. There were no Abstracts: Clinical Pharmacology and Therapeutics IXth World Congress -2008 significant differences between groups in the rate of pregnancies ending in spontaneous abortion (8.7% in exposed vs. 5.9% in unexposed; P=0.18) or in infants with minor malformations (3.7% in exposed vs. 2.9% in unexposed; P=0.61) and major malformations (3.7% in exposed vs. 2.2% in unexposed; P=0.29). No child showed features of retinoid embryopathy. In conclusion, these results bring reassurance in cases of fortuitous topical retinoid exposure. However, according to the current knowledge, topical retinoids can not be recommended for use during pregnancy, as the risk/benefit ratio remains questionable.

Pregnancy outcome following maternal exposure to statins: a multicentre prospective study.

OBJECTIVE: This contribution addresses the risk associated with exposure to statins during pregnancy. DESIGN: Multicentre observational prospective controlled study. SETTING: European Network of Teratology Information Services. POPULATION: Pregnant women who contacted one of 11 participating centres, seeking advice about exposure to statins during pregnancy, or to agents known to be nonteratogenic. METHODS: Pregnancies exposed during first trimester to statins were followed up prospectively, and their outcomes were compared with a matched control group. MAIN OUTCOME MEASURES: Rates of major birth defects, live births, miscarriages, elective terminations, preterm deliveries and gestational age and birthweight at delivery. RESULTS: We collected observations from 249 exposed pregnancies and 249 controls. The difference in the rate of major birth defects between the statin-exposed and the control groups was small and statistically nonsignificant (4.1% versus 2.7% odds ratio [OR] 1.5; 95% confidence interval [95% CI] 0.5-4.5, P = 0.43). In an adjusted Cox model, the difference between miscarriage rates was also small and not significant (hazard ratio 1.36, 95% CI 0.63-2.93, P = 0.43). Premature birth was more frequent in exposed pregnancies (16.1% versus 8.5%; OR 2.1, 95% CI 1.1-3.8, P = 0.019). Nonetheless, median gestational age at birth (39 weeks, interquartile range [IQR] 37-40 versus 39 weeks, IQR 38-40, P = 0.27) and birth weight (3280 g, IQR 2835-3590 versus 3250 g, IQR 2880-3630, P = 0.95) did not differ between exposed and non-exposed pregnancies. CONCLUSIONS: This study did not detect a teratogenic effect of statins. Its statistical power remains insufficient to challenge current recommendations of treatment discontinuation during pregnancy.

Exposure of a single host (Chrysomya megacephala) (Calliphoridae) to different quantities of female parasitoids (Nasonia vitripennis) (Pteromalidae)

The aim of this study was to verify the duration of the development period, number of parasitoids produced per pupa, parasitism rate and sex ratio of Nasonia vitripennis (Hymenoptera, Pteromalidae), when they were exposed to a single host: Chrysomya megacephala (Diptera, Calliphoridae). One pupa was exposed in glass tubes to different numbers of female parasitoids (1, 3, 5, 7, 9 and 11) during 48 h. Twenty replications/treatment were used, under controlled conditions (T= 27 °C day/ 25 °C night, 60 ± 10% RH). Statistical analysis of the data was made using the ANOVA test and the "a posteriori" comparisons were made using the Tukey-HSD test (both tests with a significance level of 5%). The duration of the development period was longer in treatments where a higher density of females per host was used. When five females per host were used, the mean number of parasitoids that emerged per pupa was higher. The data showed a tendency to a decrease in the amount of parasitoids emerged per host, especially of female, when used high quantities of female per host. Higher parasitism rates were observed in the 3:1 and 5:1 treatments and an increase in the percentage of unviable pupae was observed, probably due to an increase of female densities in the treatments, possibly a consequence of superparasitism.

Increasing lactate turnover rate during exercise by means of altitude training and fructose ingestion : effects on substrate metabolism and endurance performance

Summary : With regard to exercise metabolism, lactate was long considered as a dead-end waste product responsible for muscle fatigue and a limiting factor for motor performance. However, a large body of evidence clearly indicates that lactate is an energy efficient metabolite able to link the glycolytic pathway with aerobic metabolism and has endocrine-like actions, rather than to be a dead-end waste product. Lactate metabolism is also known to be quickly upregulated by regular endurance training and is thought to be related to exercise performance. However, to what extent its modulation can increase exercise performance in already endurance-trained subjects is unknown. The general hypothesis of this work was therefore that increasing either lactate metabolic clearance rate or lactate availability could, in turn, increase endurance performance. The first study (Study I) aimed at increasing the lactate clearance rate by means of assumed interaction effects of endurance training and hypoxia on lactate metabolism and endurance performance. Although this study did not demonstrate any interaction of training and hypoxia on both lactate metabolism and endurance performance, a significant deleterious effect of endurance training in hypoxia was shown on glucose homeostasis. The methods used to determine lactate kinetics during exercise exhibited some limitations, and the second study did delineate some of the issues raised (Study 2). The third study (Study 3) investigated the metabolic and performance effects of increasing plasma lactate production and availability during prolonged exercise in the fed state. A nutritional intervention was used for this purpose: part of glucose feedings ingested during the control condition was substituted by fructose. The results of this study showed a significant increase of lactate turnover rate, quantified the metabolic fate of fructose; and demonstrated a significant decrease of lipid oxidation and glycogen breakdown. In contrast, endurance performance appeared to be unmodified by this dietary intervention, being at odds with recent reports. Altogether the results of this thesis suggest that in endurance athletes the relationship between endurance performance and lactate turnover rate remains unclear. Nonetheless, the result of the present study raises questions and opens perspectives on the rationale of using hypoxia as a therapeutic aid for the treatment of insulin resistance. Moreover, the results of the second study open perspectives on the role of lactate as an intermediate metabolite and its modulatory effects on substrate metabolism during exercise. Additionally it is suggested that the simple nutritional intervention used in the third study can be of interest in the investigation on the aforementioned roles of lactate. Résumé : Lorsque le lactate est évoqué en rapport avec l'exercice, il est souvent considéré comme un déchet métabolique responsable de l'acidose métabolique, de la fatigue musculaire ou encore comme un facteur limitant de la performance. Or la littérature montre clairement que le lactate se révèle être plutôt un métabolite utilisé efficacement par de nombreux tissus par les voies oxydatives et, ainsi, il peut être considéré comme un lien entre le métabolisme glycolytique et le métabolisme oxydatif. De plus on lui prête des propriétés endocrines. Il est connu que l'entraînement d'endurance accroît rapidement le métabolisme du lactate, et il est suggéré que la performance d'endurance est liée à son métabolisme. Toutefois la relation entre le taux de renouvellement du lactate et la performance d'endurance est peu claire, et, de même, de quelle manière la modulation de son métabolisme peut influencer cette dernière. Le but de cette thèse était en conséquence d'investiguer de quelle manière et à quel degré l'augmentation du métabolisme du lactate, par l'augmentation de sa clearance et de son turnover, pouvait à son tour améliorer la performance d'endurance de sujets entraînés. L'objectif de la première étude a été d'augmenter la clearance du lactate par le biais d'un entraînement en conditions hypoxiques chez des cyclistes d'endurance. Basé sur la littérature scientifique existante, on a fait l'hypothèse que l'entraînement d'endurance et l'hypoxie exerceraient un effet synergétique sur le métabolisme du lactate et sur la performance, ce qui permettrait de montrer des relations entre performance et métabolisme du lactate. Les résultats de cette étude n'ont montré aucun effet synergique sur la performance ou le métabolisme du lactate. Toutefois, un effet délétère sur le métabolisme du glucose a été démontré. Quelques limitations de la méthode employée pour la mesure du métabolisme du lactate ont été soulevées, et partiellement résolues dans la seconde étude de ce travail, qui avait pour but d'évaluer la sensibilité du modèle pharmacodynamique utilisé pour le calcul du turnover du lactate. La troisième étude a investigué l'effet d'une augmentation de la lactatémie sur le métabolisme des substrats et sur la performance par une intervention nutritionnelle substituant une partie de glucose ingéré pendant l'exercice par du fructose. Les résultats montrent que les composants dynamiques du métabolisme du lactate sont significativement augmentés en présence de fructose, et que les oxydations de graisse et de glycogène sont significativement diminuées. Toutefois aucun effet sur la performance n'a été démontré. Les résultats de ces études montrent que la relation entre le métabolisme du lactate et la performance reste peu claire. Les résultats délétères de la première étude laissent envisager des pistes de travail, étant donné que l'entraînement en hypoxie est considéré comme outil thérapeutique dans le traitement de pathologies liées à la résistance à l'insuline. De plus les résultats de la troisième étude ouvrent des perspectives de travail quant au rôle du lactate comme intermédiaire métabolique durant l'exercice ainsi que sur ses effets directs sur le métabolisme. Ils suggèrent de plus que la manipulation nutritionnelle simple qui a été utilisée se révèle être un outil prometteur dans l'étude des rôles et effets métaboliques que peut revêtir le lactate durant l'exercice.

Mortality among 24,865 workers exposed to polychlorinated biphenyls (PCBs) in three electrical capacitor manufacturing plants: a ten-year update.

The objective of this analysis was to evaluate mortality among a cohort of 24,865 capacitor-manufacturing workers exposed to polychlorinated biphenyls (PCBs) at plants in Indiana, Massachusetts, and New York and followed for mortality through 2008. Cumulative PCB exposure was estimated using plant-specific job-exposure matrices. External comparisons to US and state-specific populations used standardized mortality ratios, adjusted for gender, race, age and calendar year. Among long-term workers employed 3 months or longer, within-cohort comparisons used standardized rate ratios and multivariable Poisson regression modeling. Through 2008, more than one million person-years at risk and 8749 deaths were accrued. Among long-term employees, all-cause and all-cancer mortality were not elevated; of the a priori outcomes assessed only melanoma mortality was elevated. Mortality was elevated for some outcomes of a priori interest among subgroups of long-term workers: all cancer, intestinal cancer and amyotrophic lateral sclerosis (women); melanoma (men); melanoma and brain and nervous system cancer (Indiana plant); and melanoma and multiple myeloma (New York plant). Standardized rates of stomach and uterine cancer and multiple myeloma mortality increased with estimated cumulative PCB exposure. Poisson regression modeling showed significant associations with estimated cumulative PCB exposure for prostate and stomach cancer mortality. For other outcomes of a priori interest--rectal, liver, ovarian, breast, and thyroid cancer, non-Hodgkin lymphoma, Alzheimer disease, and Parkinson disease--neither elevated mortality nor positive associations with PCB exposure were observed. Associations between estimated cumulative PCB exposure and stomach, uterine, and prostate cancer and myeloma mortality confirmed our previous positive findings.